Dr. Brian Carter, a graduate from Purdue University in clinical psychology, is a fellow in the R25 Cancer Prevention Training Program at M.D. Anderson Cancer Center. Dr. Carter has an extensive background in addiction research with a specific interest in smoking behavior. Dr. Carter's immediate goal is to use the support of the K07 to establish an independent program of research and, over the course of the award, develop a career in preventive oncology, specializing in the development of more efficacious smoking cessation treatments. The career plan includes a series of formal coursework and seminars (e.g., Human Genetics, NCI Summer Curriculum in Cancer Prevention), and the mentoring support of M.D. Anderson faculty members Drs. Paul Cinciripini (smoking cessation, physiological aspects of smoking), David Wetter (smoking cessation), Ellen Gritz (cancer prevention, tobacco control), Robert Chamberlain (cancer epidemiology), and Carl de Moor (biostatistics). M.D. Anderson, one of the leading comprehensive cancer centers in the world, has a focus on research and training with numerous didactic and collaborative opportunities. The following research is proposed. The DRD2 A1 allele has been associated with a higher prevalence of smoking, as well as smoking cessation relapse, and is believed to be associated with impaired dopaminergic function leading to an increase in negative mood. The dependence producing properties of nicotine have been related to its ability to stimulate dopamine release, which may be partly responsible for the strong relationship between smoking and mood. The startle reflex (eye blink) that follows an unexpected auditory stimulus varies in magnitude with the valence of simultaneously presented emotional cues: negative emotional cues increase blink magnitude, while positive cues reduce or inhibit the response. As such, the startle reflex is regarded as a near instantaneous measure of emotional processing. Smokers will be genotyped as carrying the DRD2 Al or A2 allele, and their mood changes (via eye blink response) as the result of acute administration of nicotine, will be assessed. These same smokers will carry, in their natural environment, a hand held computer into which they will record mood data before and after smoking a cigarette. This study will compare the mood altering profiles of nicotine, from the same sample of smokers, from both laboratory and naturalistic settings. This data will offer a more comprehensive account of the relationship between smoking and mood, and provide insight into how some smokers (based on genetic make up) may be using nicotine to regulate mood. This could provide an important assessment tool that will lead to more effective treatment plans that focus on individually targeted mood management techniques. Future studies will add to this research design a nicotine/placebo patch treatment component. Structural equation modeling will be used to design an abstinence model based on smoker variables (e.g., genetics). This model will identify which smokers benefit most (or least) from nicotine replacement. In addition, a similar research design will employ cigarette-related stimuli which will offer a more comprehensive examination of the relationships among genetics, mood, and craving for cigarettes.